1. Field of the Invention
This invention generally relates to methods of local and systemic administration of a high-density lipoprotein (HDL) for the prevention, treatment, or amelioration of a vascular disorder, disease or occlusion such as restenosis or vulnerable plaque. The invention also relates HDL coated stents or stents including HDL.
2. Description of the Background
Cholesterol is a soft, waxy substance found among the lipids (fats) in the bloodstream and in all body's cells. It is an important part of a healthy body because it is used to form cell membranes, some hormones and is needed for other functions. But a high level of cholesterol in the blood—hypercholesterolemia—is a major risk factor for coronary heart disease, which leads to heart attack.
High blood cholesterol is one of the major risk factors for heart disease. A risk factor is a condition that increases one's chance of getting a disease. In fact, the higher one's blood cholesterol level, the greater one's risk for developing heart disease or having a heart attack. Heart disease is the number one killer of women and men in the United States. Each year, more than a million Americans have heart attacks, and about a half million people die from heart disease.
Cholesterol and other fats cannot dissolve in the blood. Cholesterols have to be transported to and from the cells by special carriers called lipoproteins. There are several kinds, but the ones to focus on are low-density lipoprotein (LDL) and high-density lipoprotein (HDL).
Low-density lipoprotein is the major cholesterol carrier in the blood. If too much LDL cholesterol circulates in the blood, it can slowly build up in the walls of the arteries feeding the heart and brain. Together with other substances it can form plaque, a thick, hard deposit that can clog arteries. This condition is known as atherosclerosis. A clot (thrombus) that forms near this plaque can block the blood flow to part of the heart muscle and cause a heart attack. If a clot blocks the blood flow to part of the brain, a stroke results. A high level of LDL cholesterol reflects an increased risk of heart disease. Lower levels of LDL cholesterol reflect a lower risk of heart disease.
About one-third to one-fourth of blood cholesterol is carried by HDL. It has been documented that HDL tends to carry cholesterol away from the arteries and back to the liver, where it is passed from the body or, in the alternative, removes excess cholesterol from plaques and thus slows their growth. A low HDL level indicates a greater risk. A low HDL cholesterol level also may raise stroke risk.
It has been reported the level of serum HDL is inversely associated with the plaque size in coronary arteries (see, for example, von Bergrelen, et al., Circulation 108(22):2757-62 (2003)). U.S. Pat. Nos. 5,746,223 and 6,367,479 to Williams, for example, describe methods for increasing serum HDL level using a composition comprising large unilamellar vesicles or small unilamellar vesicles.
Steven Nissen et al., reported in November 2003 (JAMA 2003; 290: 2292-2300) that in a double-blind, randomized, placebo-controlled multicenter pilot trial, five weeks of infusion of an HDL-mimic, recombinant ApoA-I Milano/phospholipid complex could reduce 4% volume of plaque in patients with prior heart attacks. This study showed systemic delivery of HDL or HDLm may be a promising therapy to reduce plaque.
Nonetheless, there is no report on a method drawn to increase the local level of HDL at the plaque site. Nor is there any report on a method of controlled release of HDL at the plaque site.
The methods and device disclosed herein address the above described problems and needs.